Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans

International audienceParticulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled ultrafine particles are able to translocate into the bloodstream in humans. However, their conclusions were conflicting. We developed a physiologically based kinetic model for 99m-technetium-labelled carbon nanoparticles (Technegas). The model was designed to analyse imaging data. It includes different translocation rates and kinetics for free technetium, and small and large technetium-labelled particles. It was calibrated with data from an experiment designed to assess the fate of nanoparticles in humans after inhalation of Technegas. The data provided time courses of radioactivity in the liver, stomach, urine, and blood. Parameter estimation was performed in a Bayesian context with Markov chain Monte Carlo (MCMC) techniques. Our analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about twofold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation resulted in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement

Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector and agent, in Ohio

Lyme disease, the most common vector-borne disease in the United States, is caused by a tick-borne infection with Borrelia burgdorferi. Currently, Ohio is considered by the Centers for Disease Control and Prevention (CDC) to be non-endemic for Lyme disease. The low incidence of Lyme disease in this state was largely attributed to the absence of the transmitting vector, Ixodes scapularis, commonly known as the blacklegged tick. However, a tick surveillance program established by Ohio Department of Health indicated that the number of I. scapularis ticks in Ohio had increased sharply in recent years, from 0 - 5 ticks per year during 1983 - 2008 to 15 in 2009, 40 in 2010, and 184 in 2011. During the fall deer hunting season, examination of deer heads submitted to Ohio Department of Agriculture found 29 I. scapularis from 7 counties in 2010 and 1,830 from 25 counties in 2011. As of 2012, the tick had been found in 57 of the 88 counties of Ohio. In addition, all three active stages (larva, nymph, and adult) of I. scapularis were found in Tiverton Township of Coshocton County, demonstrating the presence of established tick populations at this central Ohio location. Of 530 nymphal or adult I. scapularis analyzed by quantitative polymerase chain reaction (qPCR), 32 (6.1%) tested positive for the B. burgdorferi flaB gene, ranging from 36 to 390,000 copies per tick. Antibodies to B. burgdorferi antigens were detected in 2 of 10 (20%) field-captured Peromyscus leucopus from Tiverton Township, and in 41 of 355 (11.5%) dogs residing in Ohio. Collectively, these data suggest that the enzootic life cycle of B. burgdorferi has become established in Ohio, which poses risk of Lyme disease to people and animals in the area

A Map of the Nanoworld: Sizing up the Science, Politics, and Business of the Infinitesimal

Mapping out the eight main nodes of nanotechnology discourse that have emerged in the past decade, we explore how various scientific, social, and ethical islands of discussion have developed, been recognized, and are being continually renegotiated. We do so by (1) identifying the ways in which scientists, policy makers, entrepreneurs, educators, and environmental groups have drawn boundaries on issues relating to nanotechnology; (2) describing concisely the perspectives from which these boundaries are drawn; and (3) exploring how boundaries on nanotechnology are marked and negotiated by various nodes of nanotechnology discourse.Comment: 25 page

Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

This work was funded by the Leverhulme Trust (GJF), and the Wellcome Trust (TKS, WT 093228).Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and burden to human and animal health, having the most devastating effect on the world’s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5 isoxazoles, furoxans and furazans. Several of these compounds maintain low micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.PostprintPeer reviewe

On quantum teleportation with partial entanglement

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2025, Tutor: Josep Taron RocaQuantum teleportation cannot be achieved with certainty when using a partially entangled resource; however, full-fidelity teleportation can be realized probabilistically, by allowing the protocol to fail sometimes. We present two strategies for conclusive teleportation based on generalized measurements: one involves a filtering operation applied by the receiver, while the other uses non-orthogonal state discrimination performed by the sender. Both methods are optimal in that they succeed with the maximum possible probability. Additionally, we study this maximal probability in the general d-dimensional case

The SAPUVETNET Projects: experiences of intersectoral collaboration and research/training in Veterinary Public Health across Latin America and Europe.

SAPUVETNET is the acronym of “Red de Salud Publica Veterinaria/Network of Veterinary Public Health”, a series of projects co-financed under the EU ALFA program, aimed to support an International network on Veterinary Public Health (VPH) constituted by Faculties of Veterinary Medicine from Latin-America (LA) and Europe (EU) (http://www.sapuvetnet.org). Since its start in 2002, SAPUVETNET has been continuously growing and expanding, and now it also includes several International collaborating institutions/organizations. The SAPUVETNET projects have envisaged a series of objectives/activities aimed to promote and enhance VPH research/training and intersectoral collaboration across LA and EU. Project partners use a mail-list and distance learning platforms (e.g. Moodle, Colibri) to organize common teaching activities. Major results so far achieved are: harmonisation/development of a common VPH curriculum; creation of common modules/courses on selected VPH topics; use of innovative teaching methods, based on problem solving approach/case studies; publication of videos (DVDs) and self-learning program (CD-ROM) on meat inspection/hygiene (in 3 languages); development of an on-line VPH teaching Manual (beta version in Spanish); organization of e-conferences on upcoming VPH issues; publication of a new International VPH Journal “Una Salud/One Health/Uma Saude” (in 3 languages); exchanges of teachers/researchers (e.g. bilateral visits LA-EU-LA) and coordinating meetings; participation in and/or organization of VPH seminars/congresses/conferences at National and International level; publication of scientific and popular articles on VPH issues related to project activities. SAPUVETNET didactic tools have been and/or are being tested/used by partner faculties/universities and other teaching institutions. Didactic material can be freely circulated and distributed, and can be used for distance learning, be modified/adapted to the local context of any country/geographical area, even outside LA and EU

Influences of pre- and postnatal nutritional exposures on vascular/endocrine systems in animals.

Human epidemiological and animal studies have revealed the long-term effects of malnutrition during gestation and early life on the health of the offspring. The aim of the current review is to survey the different means of achieving fetal malnutrition and its consequences, mainly in animals, and to identify key areas in which to direct future research. We address the impact of various models of a maternal protein-restricted diet and global maternal caloric restriction (either through the reduction of nutrient supply or through mechanic devices), the influence of maternal diabetes, and other maternal causes of fetal damage (maternal infections and toxic food components). More specifically, we enumerate data on how the different insults at different prenatal and early postnatal periods affect and program the development and the function of organs involved in diabetes, hypertension, and cardiovascular disease. Particular emphasis is given to the endocrine pancreas, but insulin-sensitive tissues, kidneys, and vasculature are also analyzed. Where available, the protective effects of maternal food supplementation for fetal organ development and function are discussed. Specific attention is paid to the amino acids profile, and the preventive role of taurine is discussed. Tentative indications about critical time windows for fetal development under different deleterious conditions are presented whenever possible. We also discuss future research and intervention

Nanomaterials versus ambient ultrafine particles: an opportunity to exchange toxicology knowledge

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa.info:eu-repo/semantics/publishedVersio